Bleomycin is a naturally occurring bioconjugate that has been shown to mediate sequence selective DNA and RNA cleavage. It is believed that bleomycin-induced cleavage is responsible for the drug's antitumor and antibiotic properties. In order to elucidate the molecular basis of bleomycin induced DNA/RNA cleavage, several analogs of bleomycin have been prepared. Each analog addresses a mechanistic question about a specific DNA/RNA-bleomycin interaction. It is anticipated that a comprehensive understanding of bleomycin induced DNA/RNA cleavage will facilitate the design of new structural classes of antitumor agents that employ the same mechanism of action as bleomycin. The synthesis of bleomycin analogs requires complete characterization of intermediates and final products by high resolution mass spectroscopy.